CN104774758B - The unicellular excitation of a kind of osteoblast and the MEMS system of detection - Google Patents
The unicellular excitation of a kind of osteoblast and the MEMS system of detection Download PDFInfo
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- CN104774758B CN104774758B CN201510200633.1A CN201510200633A CN104774758B CN 104774758 B CN104774758 B CN 104774758B CN 201510200633 A CN201510200633 A CN 201510200633A CN 104774758 B CN104774758 B CN 104774758B
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Abstract
The invention discloses the MEMS system of the unicellular excitation of a kind of osteoblast and detection, including: vibrationproof platform, it is positioned at the fixing device above vibrationproof platform, it is positioned at the CCD above fixing device and microscope, it is positioned at the micropositioner of fixing device, it is positioned at the secondary light source below micropositioner, it is positioned at the culture dish above micropositioner, manipulator adjusts platform and is positioned at manipulator and adjusts the manipulator above platform, described manipulator include two clamping directions relative for clamping osteoblastic test side and one between two test sides for vibrational excitation osteoblastic excitation end.The unicellular excitation of osteoblast of the present invention and the MEMS system of detection are by designing novel MEMS integrated tool, its simple in construction, it is possible to carry out osteoblastic overall situation multiple spot Dynamic and Multi dimensional detection.
Description
Technical field
The present invention relates to osteoblast excitation and detection technique field, particularly relate to a kind of unicellular excitation of osteoblast
MEMS system with detection.
Background technology
Skeletal system is one of tissue system of human body maximum, has support and protection health, maintenance motion, hemopoietic, deposits
Store up calcareous several functions of Denging.Orthopaedics illness is to affect one of population health and quality of life modal disease, with osteoporosis
As a example by disease, current China has been the country that patients with osteoporosis is most in the world, there are about patient 90,000,000, accounts for total population
7%.In China's population of more than 45 years old, every 4 male just have 1 to suffer from osteoporosis, and women sickness rate is higher, 30%
Above.Anticipated the year two thousand twenty China patients with osteoporosis is up to 2.86 hundred million, and the year two thousand fifty rises to 5.33 hundred million.Osteoblast is bone
Occur and osteoplastic Basic of Biology, be most important functioning cell in bone constantly more New activity, osteoclast number
Decline with function and bone resorption is accelerated to be osteoporotic main pathological basis.Research to cyto-mechanics characteristic, not only may be used
Think that the pathogeny of some diseases is provided fundamental basis, but also can be that its diagnosis, treatment and rehabilitation provide method.Cause
This, research osteoblast characteristic, activity change and influence factor thereof have important for the pathogenesis exploring osteoporosis
Medical significance, provide method and theoretical foundation for the diagnosis of osteoporosis, treatment and rehabilitation.
Research has turned out mechanical stress and has a great impact osteoblast vital movement.The stress research to Bone Defect Repari
More than 100 year front Wolff law can be traced back to.Osseous tissue is an optimization structure arranged by stress, and increasing stress can be direct
Stimulate the growth of bone, otherwise will result in the loss of bone.American Engineering institute academician Edmund YS Chao is in " a kind of non-wound form
Organizational project biophysics stimulate Bone Defect Repari, reconstruct, keep in effect " report in point out that physical stimulation is permissible
Help the reparation of bone, reconstruct and keep, be a kind of efficient noninvasive tissue engineering method having extensive prospect.Provided by NASA
The scientists helped and international bioastronautics research association disclose a sign, and the dither a little being barely detectable may
Stimulate bone to produce, and advise that spaceman stands in the exercise carried out 10-20 minute on micro-platform that shakes and prevent bone loss every day.Just
Often bone growth all be unable to do without mechanical stress stimulates, and in physiological activity, the stimulation of period mechanical power is the base of osteanagenesis
Plinth, wherein osteoblast is the cell sensitive to cyclic stress.As the pith in biomechanics field, osteoblast
Still need to explore further to the response mechanism of external force.
Prior art is mainly carried out body vibration be parsed into by or large batch of osteoblast overall to bone
The bone-forming effect of osteocyte, compares the most qualitative, it is impossible to quantitative analysis, it is impossible to provide accurate foundation from cell aspect.At present
The cell measurement method used also mainly is calculated by the static test result of cell surface single-point and characterizes the mechanics of cell
Characteristic, or osteoblast mechanical characteristic characterizes by method based on statistical analysis.But cell is the non-homogeneous of complexity
Body structure, the mechanical characteristic of different structure part also has difference, and therefore, multidimensional, multiple spot, the mechanics of the overall situation detect for accurately
Cell machinery mechanical response performance data measurement have absolute necessity.
Therefore, for above-mentioned technical problem, it is necessary to provide the MEMS system of the unicellular excitation of a kind of osteoblast and detection
System.
Summary of the invention
In view of this, it is an object of the invention to provide the MEMS system of the unicellular excitation of a kind of osteoblast and detection.
To achieve these goals, the technical scheme that the embodiment of the present invention provides is as follows:
The unicellular excitation of a kind of osteoblast and the MEMS system of detection, described MEMS system includes:
Vibrationproof platform, be positioned at the fixing device above vibrationproof platform, be positioned at the CCD above fixing device and microscope, be positioned at solid
Determine the micropositioner in device, be positioned at the secondary light source below micropositioner, be positioned at the culture dish above micropositioner, manipulator adjusts platform
And be positioned at manipulator and adjust the manipulator above platform, described manipulator include two clamping directions relative for clamping skeletonization
The test side of cell and one between two test sides for vibrational excitation osteoblastic excitation end.
As a further improvement on the present invention, described fixing device is fixedly installed the gripper shoe parallel with vibrationproof platform,
Described micropositioner and manipulator adjust platform and are positioned in described gripper shoe.
As a further improvement on the present invention, turntable, described micropositioner bag it are provided with between described micropositioner and gripper shoe
Include and be positioned at the first micropositioner that turntable horizontally over moves and be positioned at what the first micropositioner moved in vertical direction above
Second micropositioner.
As a further improvement on the present invention, it is whole of three bit manipulation hand adjustment that described manipulator adjusts platform, and manipulator adjusts
Platform controls manipulator and moves at three-dimensional.
The invention has the beneficial effects as follows:
The unicellular excitation of osteoblast of the present invention and the MEMS system of detection are by designing novel MEMS one chemical industry
Tool, its simple in construction, it is possible to carry out osteoblastic overall situation multiple spot Dynamic and Multi dimensional detection, set up excitation and test device realizes thin
The dynamic test of born of the same parents, analyzes parameter and the biological effects such as frequency of vibration, amplitude and osteoblast follow-up characteristic, damping characteristic
The relation of the quantizating index of (include sticking, breed, pattern, differentiation etc.) and affecting laws.
Accompanying drawing explanation
In order to be illustrated more clearly that the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
In having technology to describe, the required accompanying drawing used is briefly described, it should be apparent that, the accompanying drawing in describing below is only this
Some embodiments described in invention, for those of ordinary skill in the art, on the premise of not paying creative work,
Other accompanying drawing can also be obtained according to these accompanying drawings.
Fig. 1 is that in the embodiment of the invention, the structure of the unicellular excitation of osteoblast and the MEMS system of detection is shown
It is intended to；
Fig. 2 a is osteoblast structure and the schematic diagram estimating test point, and Fig. 2 b is the signal of multiple spot global area test point
Figure；
Fig. 3 is the unicellular excitation of osteoblast and the schematic diagram of detection in the present invention.
Detailed description of the invention
For the technical scheme making those skilled in the art be more fully understood that in the present invention, real below in conjunction with the present invention
Execute the accompanying drawing in example, the technical scheme in the embodiment of the present invention is clearly and completely described, it is clear that described enforcement
Example is only a part of embodiment of the present invention rather than whole embodiments.Based on the embodiment in the present invention, this area is common
The every other embodiment that technical staff is obtained under not making creative work premise, all should belong to present invention protection
Scope.
The invention discloses the MEMS system of the unicellular excitation of a kind of osteoblast and detection, this MEMS system includes:
Vibrationproof platform, be positioned at the fixing device above vibrationproof platform, be positioned at the CCD above fixing device and microscope, be positioned at solid
Determine the micropositioner in device, be positioned at the secondary light source below micropositioner, be positioned at the culture dish above micropositioner, manipulator adjusts platform
And be positioned at manipulator and adjust the manipulator above platform, described manipulator include two clamping directions relative for clamping skeletonization
The test side of cell and one between two test sides for vibrational excitation osteoblastic excitation end.
Ginseng Fig. 1 show the unicellular excitation of osteoblast in the embodiment of the invention MEMS system with detection
Structural representation, comprising:
Vibrationproof platform 1；
It is positioned at the fixing device 2 above vibrationproof platform 1；
It is positioned at the CCD 3 above fixing device 2 and microscope 4；
The gripper shoe 5 parallel with vibrationproof platform being positioned in fixing device 2, this gripper shoe is used for fixing micropositioner and manipulator
Adjust platform；
The turntable 6 being positioned in gripper shoe 5, micropositioner includes being positioned at what turntable 6 horizontally over (x, y direction) moved
First micropositioner 7 and be positioned at the second micropositioner 8 that the first micropositioner 7 (z direction) in vertical direction above moves；
The secondary light source 9 being positioned at below micropositioner and be fixed on vibrationproof platform 1；
It is positioned at the culture dish 10 above the second micropositioner in micropositioner, culture dish 10 is used for deposit and treats excitation and detection
Osteoblast；
Manipulator adjusts platform 11, and manipulator adjusts platform and is fixedly mounted in gripper shoe 5, and is positioned at the outside of fixing device 2.
In present embodiment, manipulator adjusts platform 11 is whole of three bit manipulation hand adjustment, and manipulator adjusts platform and controls manipulator at three-dimensional
Move；
Being positioned at manipulator and adjust the manipulator 12 above platform 11, shown in Fig. 3, manipulator includes two clamping direction phases
To be used for clamp osteoblastic test side and one and swash for vibrational excitation is osteoblastic between two test sides
Encourage end.
Owing to osteoblastic mechanical property and environmental condition, cell growth cycle are relevant, therefore for particular batch
Cell, first combines above-mentioned osteoblast each several part and simplifies the typical mechanics feature calculation method of structure, and biological characteristic ginseng
Number, the case hardness of Theoretical Calculation cell and Young's modulus, carry out osteoblast local and the emulation of overall situation mechanical property, set up
Osteoblast dynamic response model, analyzes vibrational excitation transmission in osteoblast body and damped manner, the research machinery field of force
The change affecting laws to osteoblast dynamic characteristic, assesses cell deformation characteristics in loading process.Follow-up will be by setting
The fine testing tool of meter carries out the extruding test of osteoblast surfaces multiple spot, is modified osteoblastic characteristic parameter, complete
Kind dynamic response model.
Osteoblastic dynamic characteristic detects, and is the detection process of a persistence.At above-mentioned theory analysis and model base
On plinth, for features such as osteoblastic mechanical response dynamic, serialitys in the present invention, design contact trailing type detection side
Method, feeds back the continuous process of dynamic response.Simultaneously as osteoblast is irregular organism, need to pass through multiple spot
Detection realizes overall situation dynamic characteristic and describes, and is illustrated in figure 2 the schematic diagram of osteoblast dynamic response test point, wherein, Fig. 2 a
For osteoblast structure and the schematic diagram of estimating test point, Fig. 2 b is the schematic diagram of multiple spot global area test point.
Therefore, in order to realize the motility of excitation and detection method, the design of integration is used, on detection instrument
Integrated vibrational excitation part, it is achieved the excitation of osteoblastic original position and detection.Simultaneously in order to preferably contact with cell, devise
Clipping detection instrument, can be adjusted the exposure level of tool tip and cell, and devise detection work by holding action
The two-dimentional sensing mode of tool end structure, it is achieved the dynamic detection of osteoblast overall situation multiple spot multidimensional.As it is shown on figure 3, test side
Clamping osteoblast, is fully contacted with detected part.Two dimension sensing after carrying out vibrational excitation by excitation end, on test side
Device can realize x as shown in the figure to z to dynamic response detection.Pass through Spin cells, it is possible to achieve y to z to dynamic
Response detection.
On the basis of based on MEMS integrated testing and operation instrument research, improve the control module of this MEMS system with
Vision localization module, and design the locating module that can realize four degree of freedom motions of Tissue Culture Dish, it is achieved tested skeletonization is thin
Born of the same parents' being accurately positioned under the microscope, it is possible to carry out osteoblastic selection, it is achieved multiple spot detects.For the osteoblast overall situation
Dynamically testing requirement, is optimized modular operation, checking test, and operation instrument is adjusting under platform drives and can realize
Three-dimensional motion.
In the present invention, it is selected to osteocyte and carries out sample detection, osteoblast under test different stimulated frequency, various amplitude
The Changing Pattern of mechanical response, on the basis of each group of experimental data computational analysis, establishment stage state-detection data base；Pass through
Cell culture experiments and fluorescence microscopy research osteoblast biologically (include sticking, breed, pattern, differentiation etc.), with
Shi Liyong SABC demarcates means detection important cells albumen and the change of molecule (actin, vinculin etc.), experiment is tied
Fruit is analyzed with tool detection result before, analyzes frequency of vibration, amplitude and cell damping characteristic to cell skeletonization
The affecting laws of effect, proposes cell growth state mechanics characterization method, sets up the cell vibration force environment reference being suitable for skeletonization
System, is used for the personnel of directing study and carries out osteoblastic bone-forming effect biological analysis.
Present embodiment illustrates as a example by osteoblast the principle of excitation and detection, the most also may be used
To be applied to other similar cell, this is no longer going to repeat them.
By technique scheme it can be seen that the MEMS system of the unicellular excitation of the osteoblast of the present invention and detection passes through
Design novel MEMS integrated tool, its simple in construction, it is possible to carry out osteoblastic overall situation multiple spot Dynamic and Multi dimensional detection, build
Vertical excitation and test device realize the dynamic test of cell, analyze frequency of vibration, amplitude and osteoblast follow-up characteristic, damping spy
Property etc. the relation of quantizating index of parameter and biological effect (include sticking, breed, pattern, differentiation etc.) and affecting laws.
It is obvious to a person skilled in the art that the invention is not restricted to the details of above-mentioned one exemplary embodiment, Er Qie
In the case of the spirit or essential attributes of the present invention, it is possible to realize the present invention in other specific forms.Therefore, no matter
From the point of view of which point, all should regard embodiment as exemplary, and be nonrestrictive, the scope of the present invention is by appended power
Profit requires rather than described above limits, it is intended that all by fall in the implication of equivalency and scope of claim
Change is included in the present invention.Should not be considered as limiting involved claim by any reference in claim.
Although moreover, it will be appreciated that this specification is been described by according to embodiment, but the most each embodiment only wraps
Containing an independent technical scheme, this narrating mode of description is only that for clarity sake those skilled in the art should
Description can also be formed those skilled in the art through appropriately combined as an entirety, the technical scheme in each embodiment
May be appreciated other embodiments.
Claims (3)
1. the unicellular excitation of osteoblast and the MEMS system of detection, it is characterised in that described MEMS system includes:
Vibrationproof platform, it is positioned at the fixing device above vibrationproof platform, is positioned at the CCD above fixing device and microscope, is positioned at fixing dress
Put interior micropositioner, be positioned at the secondary light source below micropositioner, be positioned at the culture dish above micropositioner, manipulator adjusts platform and
Be positioned at manipulator and adjust the manipulator above platform, described manipulator include two clamping direction relative for clamping osteoblast
Test side and one between two test sides for vibrational excitation osteoblastic excitation end, solid in described fixing device
Surely being provided with the gripper shoe parallel with vibrationproof platform, described micropositioner and manipulator adjust platform and are positioned in described gripper shoe.
The unicellular excitation of osteoblast the most according to claim 1 and the MEMS system of detection, it is characterised in that described micro-
Moving and be provided with turntable between platform and gripper shoe, described micropositioner includes being positioned at the first fine motion that turntable horizontally over moves
Platform and be positioned at the second micropositioner that the first micropositioner moves in vertical direction above.
The unicellular excitation of osteoblast the most according to claim 1 and the MEMS system of detection, it is characterised in that described behaviour
Making whole of hand adjustment is whole of three bit manipulation hand adjustment, and manipulator adjusts platform control manipulator and moves at three-dimensional.
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| CN103966091A (en) * | 2014-05-15 | 2014-08-06 | 厦门大学 | Devices for cell composite force-electric load measurement |
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| CN204608008U (en) * | 2015-04-24 | 2015-09-02 | 苏州大学 | The MEMS system of the unicellular excitation of a kind of scleroblast and detection |
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| CN103966091A (en) * | 2014-05-15 | 2014-08-06 | 厦门大学 | Devices for cell composite force-electric load measurement |
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